Funding sources This research was funded by the Wellcome Trust. N.J.S. is partly supported by the Great Ormond Street Hospital Children's Charity and the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre.
Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem-cell phenotype
Article first published online: 13 AUG 2013
© 2013 The Authors BJD © 2013 British Association of Dermatologists
British Journal of Dermatology
Volume 169, Issue 2, pages 374–383, August 2013
How to Cite
Kinsler, V.A., Anderson, G., Latimer, B., Natarajan, D., Healy, E., Moore, G.E. and Sebire, N.J. (2013), Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem-cell phenotype. British Journal of Dermatology, 169: 374–383. doi: 10.1111/bjd.12323
Conflicts of interest None declared.
- Issue published online: 13 AUG 2013
- Article first published online: 13 AUG 2013
- Accepted manuscript online: 21 MAR 2013 12:24AM EST
- Manuscript Accepted: 12 MAR 2013
Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations; however, the lineage of the mutated cells remains uncertain.
To test the hypothesis that CMN may be derived from cutaneous stem cells.
Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (nestin, fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67) and MTOR/Wnt-signalling pathway activation (pS6, β-catenin). Semiquantitative scoring compared samples with naevus cell nesting (group 1) with those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples.
A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and was stronger superficially. Expression of β-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli.
Congenital melanocytic naevi development frequently coexists with normal overlying melanocyte development, leading us to hypothesize that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem-cell origin, capable of some degree of melanocytic differentiation superficially.